Faculty Profile

Sridhar Mani, M.D.

Professional Interests

Orphan nuclear receptors (those that lack a well defined physiologic ligand) control nearly every major physiologic and biochemical process in eukaryotes - cell metabolism (e.g., cholesterol, energy, bile acids), xenobiotic detoxification, cell differentiation (e.g., gastrulation, retinal development), circadian rhythm, and cancer cell growth and apoptosis (e.g., NURR77). Of these receptors, the steroid and xenobiotic receptor (SXR) is a key regulator of genes encoding drug metabolizing and transport proteins. In addition, SXR has been implicated in cancer drug resistance, carcinogenesis, innate immunity, infection control and pathophysiologic states like osteomalacia. Our laboratory focuses on defining the role of SXR and other orphans by using novel and dynamic models of human pathophysiology in (i) xenobiotic metabolism and pharmacology; (ii) carcinogenesis, organogenesis and anticancer drug resistance and (iii) innate immunity.

Recently, our laboratory has directed interests in the mammalian microbiome. We have discovered a novel link between the microbial metabolome and orphan nuclear receptor, SXR/PXR (Immunity, 2014). Further work in the laboratory is focussed on defining how the microbial environment shapes health and disease.

Contact

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